Journal Article

UV-enhanced reactivation of a UV-damaged reporter gene suggests transcription-coupled repair is UV-inducible in human cells

Murray A. Francis and Andrew J. Rainbow

in Carcinogenesis

Volume 20, issue 1, pages 19-26
Published in print January 1999 | ISSN: 0143-3334
Published online January 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.1.19
UV-enhanced reactivation of a UV-damaged reporter gene suggests transcription-coupled repair is UV-inducible in human cells

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The genetic disorders xeroderma pigmentosum (XP) and Cockayne syndrome (CS) exhibit deficiencies in the repair of UV-induced DNA damage. CS fibroblasts retain proficient nucleotide excision repair (NER) of inactive (or bulk) DNA, but are deficient in the transcription-coupled repair (TCR) of active genes. In contrast, XP complementation group C (XP-C) fibroblasts retain proficient TCR, but are deficient in bulk DNA repair. The remaining NER-deficient XP groups exhibit deficiencies in both repair pathways. Ad5HCMVsp1lacZ is a recombinant adenovirus vector that is unable to replicate in human fibroblasts, but can efficiently infect and express the β-galactosidase reporter gene in these cells. We have examined the host cell reactivation (HCR) of β-galactosidase activity for UV-irradiated Ad5HCMVsp1lacZ in non-irradiated and UV-irradiated normal, XP-B, XP-C, XP-D, XP-F, XP-G, CS-A and CS-B fibroblasts. HCR of β-galactosidase activity for UV-irradiated Ad5HCMVsp1lacZ was reduced in non-irradiated cells from each of the repair-deficient groups examined (including XP-C) relative to that in non-irradiated normal cells. Prior irradiation of cells with low UV fluences resulted in an enhancement of HCR for normal and XP-C strains, but not for the remaining XP and CS strains. HCR of the UV-damaged reporter gene in UV-irradiated XP and CS strains was similar to measurements of TCR reported previously for these cells. These results suggest that UV treatment results in an induced repair of UV-damaged DNA in the transcribed strand of an active gene in XP-C and normal cells through an enhancement of TCR or a mechanism which involves the TCR pathway.

Keywords: Ad, adenovirus; α-MEM, α-minimal essential medium; β-gal, β-galactosidase; CS, Cockayne syndrome; HCMV, human cytomegalovirus; HCR, host cell reactivation; JNK, c-jun N-terminal kinase; NER, nucleotide excision repair; RNAPII, RNA polymerase II; TCR, transcription-coupled repair; BER, base excision repair; XP, xeroderma pigmentosum.

Journal Article.  7254 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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